Synthesis
The general procedure for the synthesis of ethyl [2-phenyl-2-oxoethyl]amino-2-oxoacetate from 2-aminoacetophenone hydrochloride and ethyl oxalyl chloride monoethyl ester was as follows: triethylamine (36 mL, 262.1 mmol) was slowly added to an anhydrous dichloromethane (300 mL) solution of 2-aminoacetophenone hydrochloride (15.0 g, 87.39 mmol) at 0 °C. This was followed by dropwise addition of ethyl oxalyl chloride monoethyl ester (10 mL, 87.39 mmol). The reaction mixture was gradually warmed to room temperature and stirred continuously for 16 hours. Upon completion of the reaction, the mixture was diluted with water and extracted with ethyl acetate. The organic phases were combined, washed sequentially with water and saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography (60-120 mesh, eluent was 20-30% petroleum ether solution of ethyl acetate) to afford the target compound [2-phenyl-2-oxoethyl]amino-2-oxoacetic acid ethyl ester (13.5 g, 66% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3) and mass spectrometry (ESI): 1H NMR δ 8.09 (br s, 1H), 8.02-8.00 (m, 2H), 7.68-7.64 (m, 1H), 7.55-7.51 (m, 2H), 4.85-4.84 (d, J = 4.9 Hz, 2H), 4.44 -4.39 (q, J = 7.0 Hz, 2H), 1.44-1.41 (t, J = 7.2 Hz, 3H); MS (ESI) m/z: [M + H]+ calculated 235.08, measured 236.2.
References
[1] Patent: EP2533783, 2015, B1. Location in patent: Paragraph 0609-0610
[2] Patent: WO2018/58148, 2018, A1. Location in patent: Paragraph 0256
[3] Chemische Berichte, 1914, vol. 47, p. 3166
[4] Patent: WO2005/61510, 2005, A1. Location in patent: Page/Page column 16-17
[5] Patent: WO2017/103614, 2017, A1. Location in patent: Page/Page column 62
